Recent progress in human telomerase structure and its therapeutic targeting

Most cancer and stem cells activate telomerase to preserve critical genetic material during cell division. Telomerase is a reverse transcriptase ribonucleoprotein that adds telomeric repeats to chromosome ends, thus overcoming the end-replication problem. Shortening of telomeric repeats, or telomeres, is associated with genomic instability, cancer, and aging. Telomerase dysfunction during early development leads to telomeropathies such as dyskeratosis congenita, pulmonary fibrosis, and aplastic anaemia. Recent advancements in cryo-electron microscopy and improved strategies for purifying human telomerase have laid a strong foundation in the structural biology of telomerase, advancing our understanding of its molecular interactome. In this report, we review the latest progress in human telomerase structure and outline emerging therapeutic strategies targeting telomerase.